MRI surgical systems including MRI-compatible surgical cannulae for transferring a substance to and/or from a patient

ABSTRACT

A cannula for transferring a substance to and/or from a patient includes a tubular support sleeve and a transfer tube. The support sleeve includes a rigid tubular member defining a lumen extending from a proximal end to a distal end of the tubular member. The transfer tube is positioned in the lumen and extends beyond each of the proximal end and the distal end of the tubular member. The tubular member includes a rigid, MRI-compatible material.

RELATED APPLICATION INFORMATION

This application is a 35 U.S.C. § 371 national stage filing of PCTInternational Application No. PCT/US2011/031678, filed Apr. 8, 2011,which claims the benefit of U.S. Provisional Patent Application No.61/324,990, filed Apr. 16, 2010, the disclosures of which areincorporated herein by reference in their entireties.

FIELD OF THE INVENTION

The present invention relates to MRI-guided diagnostic or interventionalsystems that may be particularly suitable for placement/localization oftherapies in the body.

BACKGROUND OF THE INVENTION

Various therapeutic and diagnostic procedures require that a substancebe infused into a prescribed region of a patient, such as into a targetdeep brain location in the patient's brain, using a delivery cannula. Itis often important or critical that the substance be delivered with highaccuracy to the target region in the patient and without undue trauma tothe patient. Moreover, it may be desirable to control or alter aspectsof the flow of the substance into the target region from the deliverycannula.

SUMMARY OF THE INVENTION

According to embodiments of the present invention, a cannula fortransferring a substance to and/or from a patient includes a tubularsupport sleeve and a transfer tube. The support sleeve includes a rigidtubular member defining a lumen extending from a proximal end to adistal end of the tubular member. The transfer tube is positioned in thelumen and extends beyond each of the proximal end and the distal end ofthe tubular member. The tubular member comprises a rigid, MRI-compatiblematerial.

According to some embodiments, the tubular member comprises a ceramicmaterial.

In some embodiments, the cannula includes a conformal polymeric sleevesurrounding the tubular member. According to some embodiments, theconformal polymeric sleeve is a polymeric shrink tubing.

According to some embodiments, an exterior surface of the cannula has atleast first and second co-axially disposed segments having differentouter diameters. In some embodiments, the exterior surface includes atapered transition between the first and second segments.

The cannula may include a second tubular member disposed in the firsttubular member and extending beyond the distal end of the first tubularmember, wherein the transfer tube extends beyond a distal end of thesecond tubular member.

In some embodiments, the transfer tube is formed of fused silica.

According to some embodiments, the tubular member has a length of atleast 10 inches.

In some embodiments, an outer surface of the tubular member has a sizeand geometry adapted for use with a stereotactic frame.

According to embodiments of the present invention, a cannula fortransferring a substance to and/or from a patient includes a tubularsupport sleeve. The support sleeve includes a rigid tubular memberdefining a lumen extending from a proximal end to a distal end of thetubular member. An exterior surface of the cannula has at least firstand second co-axially disposed segments having different outerdiameters. The tubular member comprises a ceramic material.

According to method embodiments of the present invention, a method oftransferring a substance to and/or from a patient includes: providing acannula including a rigid tubular member defining a lumen, wherein thetubular member comprises a ceramic material; inserting the cannula intoa selected region in the patient; and transferring the substance to orfrom the selected region through the lumen.

In some embodiments, the selected region is the brain.

According to embodiments of the present invention, a cannula fortransferring a substance to and/or from a patient includes a rigidtubular support sleeve defining a lumen extending from a proximal end toa distal end thereof. An exterior surface of the cannula has at leastfirst and second co-axially disposed segments having different outerdiameters. The exterior surface includes a tapered transition betweenthe first and second segments.

According to embodiments of the present invention, a cannula fortransferring a substance to and/or from a patient includes a rigidtubular support sleeve and a transfer tube. The support sleeve defines alumen extending from a proximal end to a distal end thereof. Thetransfer tube is positioned in the lumen and extends beyond each of theproximal end and the distal end of the tubular support sleeve. Thetransfer tube has an inner diameter of about 200 micrometers.

According to embodiments of the present invention, a cannula fortransferring a substance to and/or from a patient defines a lumenextending from a proximal end to a distal end thereof. An exteriorsurface of the cannula has at least first, second and third co-axiallydisposed segments having different outer diameters, the outer diameterof the second segment being greater than the outer diameter of the firstsegment and the outer diameter of the third segment being greater thanthe outer diameter of the second segment. The first segment extends fromthe distal terminus of the cannula from which the substance is dispensedin use. The second segment extends between and adjoins each of the firstand third segments. The length of the second segment is about 15 mm.

According to embodiments of the present invention, a cannula fortransferring a substance to and/or from a patient includes a rigidtubular support sleeve, a transfer tube, and silicone or PVC protectivetubing. The support sleeve defines a lumen extending from a proximal endto a distal end thereof. The transfer tube is positioned in the lumenand extends beyond each of the proximal end and the distal end of thetubular support sleeve. The protective tubing extends from the proximalend of the tubular support sleeve and surrounds the portion of thetransfer tube extending beyond the proximal end of the tubular supportsleeve.

According to embodiments of the present invention, an MRI-guidedsurgical system for delivering a substance to a patient includes anMRI-compatible delivery cannula, a circuit and at least one display. Thedelivery cannula is configured to deliver the substance to a selectedregion in the patient. The circuit is adapted to communicate with an MRIscanner. The circuit automatically segments MR image data provided bythe MRI scanner. The at least one display is in communication with thecircuit. The circuit is configured to generate and displayvisualizations of the substance registered to patient anatomicalstructure in near real-time to facilitate the MRI-guided surgicalprocedure.

According to method embodiments of the present invention, a method fordelivering a substance to a patient in an MRI-guided surgical procedureincludes: delivering the substance to a selected region in the patientusing an MRI-compatible delivery cannula; obtaining MRI image data ofthe patient; automatically segmenting the MRI image data; and generatingand displaying visualizations of the delivered substance registered topatient anatomical structure in near real-time. The visualizationsfacilitate the MRI-guided surgical procedure.

According to some embodiments, the step of generating and displayingvisualizations of the delivered substance registered to the patientanatomical structure in near real-time includes visually showing adynamic dispersion and/or infusion pattern.

According to embodiments of the present invention, an MRI-guidedsurgical system for transferring a substance to and/or from a patientincludes an MRI-compatible cannula, a circuit and at least one display.The MRI-compatible cannula is configured to transfer the substance to orfrom a selected region in the patient. The circuit is adapted tocommunicate with an MRI scanner. The circuit automatically segments MRimage data provided by the MRI scanner. The at least one display is incommunication with the circuit. The circuit is configured to generateand display visualizations of the cannula registered to patientanatomical structure in near real-time to facilitate the MRI-guidedsurgical procedure.

According to some embodiments, the circuit is configured to generate anddisplay visualizations of the delivered substance registered to thepatient anatomical structure in near real-time to visually show adynamic dispersion and/or infusion pattern of the delivered substance.

According to embodiments of the present invention, a method fortransferring a substance to and/or from a patient in an MRI-guidedsurgical procedure includes: transferring the substance to or from aselected region in the patient using an MRI-compatible cannula;obtaining MRI image data of the patient; automatically segmenting theMRI image data; and generating and displaying visualizations of thecannula registered to patient anatomical structure in near real-time.The visualizations facilitate the MRI-guided surgical procedure.

According to embodiments of the present invention, an MRI-guidedsurgical system for transferring a substance to and/or from a patientincludes an MRI-compatible cannula, a circuit, and at least one display.The MRI-compatible cannula is configured to transfer the substance to orfrom a selected region in the patient. The cannula includes anadjustment feature to selectively vary at least one characteristic ofthe flow of the substance dispensed from or drawn into the cannula. Thecircuit is adapted to communicate with an MRI scanner. The at least onedisplay is in communication with the circuit. The circuit is configuredto generate and display visualizations of the cannula and/or thesubstance in near real-time to facilitate the MRI-guided surgicalprocedure.

In some embodiments, the cannula has predefined physical characteristicsknown to the circuit and/or an operator and which can be used to assessa setting of the adjustment feature. According to some embodiments, thecircuit electronically recognizes the predefined physicalcharacteristics of the cannula and is operable to evaluate MR image datafrom the MRI scanner to assess the setting of the adjustment feature.

According to some embodiments, the circuit is configured toelectronically generate directions on adjustments to the cannula usingthe adjustment feature to obtain a new setting of the adjustmentfeature.

In some embodiments, the at least one characteristic of the flow of thesubstance dispensed from or drawn into the cannula includes a flow rateand/or a flow pattern of the flow of the substance dispensed from thedelivery cannula.

According to method embodiments of the present invention, a method fordelivering a substance to a patient in an MRI-guided surgical procedureincludes: delivering the substance to a selected region in the patientusing an MRI-compatible delivery cannula, the delivery cannula includingan adjustment feature; obtaining MR image data of the patient; andadjusting at least one characteristic of the flow of the substancedispensed from the delivery cannula using the adjustment feature and theMR image data.

In some embodiments, the foregoing method includes generating anddisplaying visualizations of the delivery cannula and/or the substancein near real-time to facilitate the MRI-guided surgical procedure.

According to method embodiments of the present invention, a method fortransferring a substance to and/or from a patient in an MRI-guidedsurgical procedure includes: mounting an MRI-compatible intrabodysurgical cannula on an MRI-compatible guide frame; selectivelypositioning the intrabody surgical cannula with respect to the patientusing the guide frame; obtaining MRI image data of the patient; andgenerating and displaying visualizations of the intrabody surgicalcannula and/or the guide frame registered to patient anatomicalstructure, wherein the visualizations facilitate the MRI-guided surgicalprocedure.

In some embodiments, the method includes delivering the substancethrough the intrabody surgical cannula into the patient.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of a MRI-guided surgical systemaccording to some embodiments of the present invention.

FIG. 2 is a side perspective view of a trajectory guide forming a partof the MRI-guided surgical system of FIG. 1 mounted on a patient.

FIG. 3 is a side perspective view of a part of the MRI-guided surgicalsystem of FIG. 1 mounted on the patient.

FIG. 4 is an enlarged, perspective view of the trajectory guide of FIG.2.

FIG. 5 is a sectional view of the trajectory guide of FIG. 2 with asurgical cannula forming a part of the MRI-guided surgical systemaccording to embodiments of the present invention.

FIGS. 6A-6C and 7A-7B are schematic illustrations of exemplary screenshots of displays of a User Interface provided to a user to facilitatenavigation and/or assessment steps of an MRI-guided infusion procedure.

FIG. 8 is a cross-sectional view of a surgical cannula according to someembodiments of the present invention.

FIG. 9A is an exploded view of a surgical cannula according to furtherembodiments of the present invention.

FIG. 9B is a cross-sectional view of the assembled surgical cannula ofFIG. 9A.

FIG. 10 is a fragmentary, side view of a surgical cannula according tofurther embodiments of the present invention.

FIG. 11 is a fragmentary, side view of a surgical cannula according tofurther embodiments of the present invention.

FIG. 12A is a side view of a surgical cannula according to furtherembodiments of the present invention.

FIG. 12B is a cross-sectional view of the surgical cannula of FIG. 12Ataken along the line 12B-12B of FIG. 12A.

FIG. 12C is an enlarged, cross-sectional view of Detail 12C of FIG. 12B.

FIG. 12D is an enlarged, cross-sectional view of Detail 12D of FIG. 12B.

FIG. 12E is an enlarged, cross-sectional view of Detail 12E of FIG. 12B.

FIG. 13 is a cross-sectional view of a targeting cannula with a surgicalcannula and an adapter.

FIG. 14A is a schematic illustration of a chronic substance deliverysystem according to some embodiments of the present invention.

FIG. 14B is a schematic illustration of a portion of the chronicsubstance delivery system of FIG. 14A with an access port thereof beingclosed.

FIG. 15 is a data processing system according to some embodiments of thepresent invention.

FIG. 16 is an exemplary screen shot of a display of a User Interfaceduring an MRI-guided infusion procedure.

FIGS. 17A and 17B are exemplary screen shots of a display of a UserInterface during an MRI-guided infusion procedure and captured at afirst time and a second, subsequent time, respectively.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

The present invention will now be described more fully hereinafter withreference to the accompanying drawings, in which embodiments of theinvention are shown. This invention may, however, be embodied in manydifferent forms and should not be construed as limited to theembodiments set forth herein; rather, these embodiments are provided sothat this disclosure will be thorough and complete, and will fullyconvey the scope of the invention to those skilled in the art. Likenumbers refer to like elements throughout. It will be appreciated thatalthough discussed with respect to a certain embodiment, features oroperation of one embodiment can apply to others.

In the drawings, the thickness of lines, layers, features, componentsand/or regions may be exaggerated for clarity and broken lines (such asthose shown in circuit of flow diagrams) illustrate optional features oroperations, unless specified otherwise. In addition, the sequence ofoperations (or steps) is not limited to the order presented in theclaims unless specifically indicated otherwise.

The terminology used herein is for the purpose of describing particularembodiments only and is not intended to be limiting of the invention. Asused herein, the singular forms “a”, “an” and “the” are intended toinclude the plural forms as well, unless the context clearly indicatesotherwise. It will be further understood that the terms “comprises”and/or “comprising,” when used in this specification, specify thepresence of stated features, steps, operations, elements, and/orcomponents, but do not preclude the presence or addition of one or moreother features, steps, operations, elements, components, and/or groupsthereof. As used herein, the term “and/or” includes any and allcombinations of one or more of the associated listed items.

Unless otherwise defined, all terms (including technical and scientificterms) used herein have the same meaning as commonly understood by oneof ordinary skill in the art to which this invention belongs. It will befurther understood that terms, such as those defined in commonly useddictionaries, should be interpreted as having a meaning that isconsistent with their meaning in the context of the specification andrelevant art and should not be interpreted in an idealized or overlyformal sense unless expressly so defined herein. Well-known functions orconstructions may not be described in detail for brevity and/or clarity.

It will be understood that when a feature, such as a layer, region orsubstrate, is referred to as being “on” another feature or element, itcan be directly on the other element or intervening elements may also bepresent. In contrast, when an element is referred to as being “directlyon” another feature or element, there are no intervening elementspresent. It will also be understood that, when a feature or element isreferred to as being “connected” or “coupled” to another feature orelement, it can be directly connected to the other element orintervening elements may be present. In contrast, when a feature orelement is referred to as being “directly connected” or “directlycoupled” to another element, there are no intervening elements present.Although described or shown with respect to one embodiment, the featuresso described or shown can apply to other embodiments.

The term “electroanatomical visualization” refers to a visualization ormap of the anatomical structure, e.g., brain, typically a volumetric,3-D map or 4-D map, that illustrates or shows electrical activity oftissue correlated to anatomical and/or coordinate spatial position. Thevisualization can be in color and color-coded to provide an easy tounderstand map or image with different measures or gradients of activityin different colors and/or intensities. The term “color-coded” meansthat certain features, electrical activity or other output are shownwith defined colors of different color and/or intensity to visuallyaccentuate different tissue, different and similar electrical activityor potential in tissue and/or to show abnormalities or lesions in tissueversus normal or non-lesion tissue. In some embodiments, the systems canbe configured to allow a clinician to increase or decrease the intensityor change a color of certain tissue types or electrical outputs, e.g.,in high-contrast color and/or intensity, darker opacity or the like.

The actual visualization can be shown on a screen or display so that themap and/or anatomical or tool structure is in a flat 2-D view and/or in2-D what appears to be 3-D volumetric images with data representingfeatures or electrical output with different visual characteristics suchas with differing intensity, opacity, color, texture and the like. Forexample, the 3-D image of the lung can be generated to illustratedifferences in barrier thickness using color or opacity differences overthe image volume. Thus, the term “3-D” in relation to images does notrequire actual 3-D viewability (such as with 3-D glasses), just a 3-Dappearance, typically on a display. The 3-D images comprise multiple 2-Dslices. The 3-D images can be volume renderings well known to those ofskill in the art and/or a series of 2-D slices, which can be visuallypaged through. A 4-D map illustrates time-dependent activity, such aselectrical activity or blood flow movement.

The surgical systems may be configured to operate based on knownphysical characteristics of one or more surgical tools, which mayinclude a surgical (e.g., delivery) cannula, such that the hardware is apoint of interface for the circuit or software. The systems cancommunicate with databases that define dimensions, configurations orshapes and spacing of components on the tool(s). The defined physicaldata can be obtained from a CAD model of a tool. The physicalcharacteristics can include dimensions or other physical features orattributes and may also include relative changes in position of certaincomponents or features upon a change in position of a tool or portionthereof. The defined physical characteristics can be electronically(programmatically) accessible by the system or known a priori andelectronically stored locally or remotely and used to automaticallycalculate certain information and/or to segment image data. That is,tool data from the known dimensions and configuration of the tool modelcan be used to segment image data and/or correlate a position andorientation of a tool and/or provide trajectory adjustment guidelines orerror estimates, warnings of improper trajectories and the like. Forexample, the system can include defined structural and/or operationaldetails/data for one or more of a delivery cannula, a grid for marking aburr hole location and/or a trajectory guide. The system can use thisdata to allow a user to adjust an intrabrain path for placing adiagnostic or therapy device. Such can be input, transposed, and/oroverlayed in a visualization of the tool on one or more displays alongwith patient structure or otherwise used, such as, for example, toproject the information onto a patient's anatomical structure ordetermine certain operational parameters including which image volume(scan planes) to use to obtain MRI image data that will include selectportions of the targeting cannula or surgical cannula. As such, at leastsome of the generated visualizations are not merely an MRI image of thepatient during a procedure.

The visualizations are rendered visualizations that can combine multiplesources of data to provide visualizations of spatially encoded toolposition and orientation with anatomical structure and can be used toprovide position adjustment data output so that a clinician can obtain adesired trajectory path, thereby providing a smart-adjustment systemwithout requiring undue “guess” work on what adjustments to make toobtain the desired trajectory.

The term “animation” refers to a sequence or series of images shown insuccession, typically in relatively quick succession, such as in about1-50 frames per second. The term “frame” refers to a singlevisualization or static image. The term “animation frame” refers to oneimage frame of the different images in the sequence of images.

The term “ACPC coordinate space” refers to a right-handed coordinatesystem defined by anterior and posterior commissures (AC, PC) andMid-Sagittal plane points, with positive directions corresponding to apatient's anatomical Right, Anterior and Head directions with origin atthe mid-commissure point.

The term “grid” refers to a pattern of crossed lines or shapes used as areference for locating points or small spaces, e.g., a series of rowsand intersecting columns, such as horizontal rows and vertical columns(but orientations other than vertical and horizontal can also be used).The grid can include associated visual indicia such as alphabeticalmarkings (e.g., A-Z and the like) for rows and numbers for columns(e.g., 1-10) or the reverse. Other marking indicia may also be used. Thegrid can be provided as a flexible patch that can be releasably attachedto the skull of a patient. For additional description of suitable griddevices, see co-pending, co-assigned U.S. patent application Ser. No.12/236,621 (U.S. Published Patent Application No. US-2009-00177077-A1),the disclosure of which is incorporated herein by reference.

The term “fiducial marker” refers to a marker that can be electronicallyidentified using image recognition and/or electronic interrogation ofMRI image data. The fiducial marker can be provided in any suitablemanner, such as, but not limited to, a geometric shape of a portion ofthe tool, a component on or in the tool, a coating or fluid-filledcomponent or feature (or combinations of different types of fiducialmarkers) that makes the fiducial marker(s) MRI-visible with sufficientsignal intensity (brightness) or generates a “void” or dark space foridentifying location and/or orientation information for the tool and/orcomponents thereof in space.

The term “MRI scanner” refers to a magnetic resonance imaging and/or NMRspectroscopy system. As is well known, MRI scanners include a low fieldstrength magnet (typically between about 0.1 T to about 0.5 T), a mediumfield strength magnet, or a high-field strength super-conducting magnet,an RF pulse excitation system, and a gradient field system. MRI scannersare well known to those of skill in the art. Examples of commerciallyavailable clinical MRI scanners include, for example, those provided byGeneral Electric Medical Systems, Siemens, Philips, Varian, Bruker,Marconi, Hitachi and Toshiba. The MRI systems can be any suitablemagnetic field strength, such as, for example, about 1.5 T or about 3.0T, and may include other high-magnetic field systems between about 2.0T-10.0 T.

The term “RF safe” means that the lead or probe is configured to safelyoperate when exposed to RF signals, particularly RF signals associatedwith MRI systems, without inducing unplanned current that inadvertentlyunduly heats local tissue or interferes with the planned therapy.

The term “MRI visible” means that the device is visible, directly orindirectly, in an MRI image. The visibility may be indicated by theincreased SNR of the MRI signal proximate the device.

The term “MRI compatible” means that the so-called component(s) issuitable for use in an MRI environment and as such is typically made ofa non-ferromagnetic MRI compatible material(s) suitable to reside and/oroperate in or proximate a conventional medical high magnetic fieldenvironment. The “MRI compatible” component or device is “MR safe” whenused in the MRI environment and has been demonstrated to neithersignificantly affect the quality of the diagnostic information nor haveits operations affected by the MR system at the intended use position inan MR system. These components or devices may meet the standards definedby ASTM F2503-05. See, American Society for Testing and Materials (ASTM)International, Designation: F2503-05. Standard Practice for MarkingMedical Devices and Other Items for Safety in the Magnetic ResonanceEnvironment. ASTM International, West Conshohocken, Pa., 2005.

The term “near real time” refers to both low latency and high framerate. Latency is generally measured as the time from when an eventoccurs to display of the event (total processing time). For tracking,the frame rate can range from between about 100 fps to the imaging framerate. In some embodiments, the tracking is updated at the imaging framerate. For near ‘real-time’ imaging, the frame rate is typically betweenabout 1 fps to about 20 fps, and in some embodiments, between about 3fps to about 7 fps. The low latency required to be considered “near realtime” is generally less than or equal to about 1 second. In someembodiments, the latency for tracking information is about 0.01 s, andtypically between about 0.25-0.5 s when interleaved with imaging data.Thus, with respect to tracking, visualizations with the location,orientation and/or configuration of a known intrabody device can beupdated with low latency between about 1 fps to about 100 fps. Withrespect to imaging, visualizations using near real time MR image datacan be presented with a low latency, typically within between about 0.01ms to less than about 1 second, and with a frame rate that is typicallybetween about 1-20 fps. Together, the system can use the tracking signaland image signal data to dynamically present anatomy and one or moreintrabody devices in the visualization in near real-time. In someembodiments, the tracking signal data is obtained and the associatedspatial coordinates are determined while the MR image data is obtainedand the resultant visualization(s) with the intrabody device (e.g.,surgical cannula) and the near RT MR image(s) are generated.

The term “automatically” means that the operation can be substantially,and typically entirely, carried out without human or manual input, andis typically programmatically directed or carried out. The term“electronically” includes both wireless and wired connections betweencomponents. The term “programmatically” means under the direction of acomputer program that communicates with electronic circuits and otherhardware and/or software.

The term “surgical cannula” refers to an intrabody cannula used totransfer a substance to and/or from a target intrabody location.

Embodiments of the invention may be particularly suitable for use withhuman patients but may also be used with any animal or other mammaliansubject.

Embodiments of the present invention may take the form of an entirelysoftware embodiment or an embodiment combining software and hardwareaspects, all generally referred to herein as a “circuit” or “module.” Insome embodiments, the circuits include both software and hardware andthe software is configured to work with specific hardware with knownphysical attributes and/or configurations. Furthermore, the presentinvention may take the form of a computer program product on acomputer-usable storage medium having computer-usable program codeembodied in the medium. Any suitable computer readable medium may beutilized including hard disks, CD-ROMs, optical storage devices, atransmission media such as those supporting the Internet or an intranet,or other storage devices.

Computer program code for carrying out operations of the presentinvention may be written in an object oriented programming language suchas Java®, Smalltalk or C++. However, the computer program code forcarrying out operations of the present invention may also be written inconventional procedural programming languages, such as the “C”programming language. The program code may execute entirely on theuser's computer, partly on the user's computer, as a stand-alonesoftware package, partly on the user's computer and partly on anothercomputer, local and/or remote or entirely on the other local or remotecomputer. In the latter scenario, the other local or remote computer maybe connected to the user's computer through a local area network (LAN)or a wide area network (WAN), or the connection may be made to anexternal computer (for example, through the Internet using an InternetService Provider).

Embodiments are described in part below with reference to flowchartillustrations and/or block diagrams of methods, apparatus (systems) andcomputer program products according to embodiments of the invention. Itwill be understood that each block of the flowchart illustrations and/orblock diagrams, and combinations of blocks in the flowchartillustrations and/or block diagrams, can be implemented by computerprogram instructions. These computer program instructions may beprovided to a processor of a general purpose computer, special purposecomputer, or other programmable data processing apparatus to produce amachine, such that the instructions, which execute via the processor ofthe computer or other programmable data processing apparatus, createmeans for implementing the functions/acts specified in the flowchartand/or block diagram block or blocks. These computer programinstructions may also be stored in a computer-readable memory that candirect a computer or other programmable data processing apparatus tofunction in a particular manner, such that the instructions stored inthe computer-readable memory produce an article of manufacture includinginstruction means which implement the function/act specified in theflowchart and/or block diagram block or blocks.

The computer program instructions may also be loaded onto a computer orother programmable data processing apparatus to cause a series ofoperational steps to be performed on the computer or other programmableapparatus to produce a computer implemented process such that theinstructions which execute on the computer or other programmableapparatus provide steps for implementing the functions/acts specified inthe flowchart and/or block diagram block or blocks.

The flowcharts and block diagrams of certain of the figures hereinillustrate exemplary architecture, functionality, and operation ofpossible implementations of embodiments of the present invention. Inthis regard, each block in the flow charts or block diagrams representsa module, segment, or portion of code, which comprises one or moreexecutable instructions for implementing the specified logicalfunction(s). It should also be noted that in some alternativeimplementations, the functions noted in the blocks may occur out of theorder noted in, the figures. For example, two blocks shown in successionmay in fact be executed substantially concurrently or the blocks maysometimes be executed in the reverse order or two or more blocks may becombined, depending upon the functionality involved.

Some embodiments of the present invention are directed to MRI-guidedsystems that can generate substantially real time (e.g., near real-time)patient-specific visualizations of the patient and one or more surgicaltools, including an MRI-compatible intrabody surgical cannula (e.g.,delivery cannula) and the delivery distribution, location, pattern,etc., in logical space and provide feedback to a clinician to improvethe speed and/or reliability of an intrabody infusion or delivery of asubstance to a target within the body through the delivery cannula. Thedelivery cannula has at least one lumen and at least one exit portconfigured to direct a flow of the substance through the lumen and theexit port to the target.

Some embodiments of the present invention are directed to MRI-guidedsystems that can generate substantially real time patient-specificvisualizations of the patient and a distribution of a substancedelivered to a target within the patient through an MRI-compatibledelivery cannula in logical space and provide feedback to a clinician toimprove the speed and/or reliability of an intrabody infusion ordelivery of the substance. These systems can show a dynamic dispersionand/or infusion pattern of the substance infused into the patient. MRIcan be effectively used to monitor the efficacy and/or delivery of thesubstance from the delivery cannula.

The visualizations can be based (in-part) on predefined data of thedelivery cannula which can define a point of interface for the system(e.g., software) based on predefined characteristics of the deliverycannula, e.g., dimensions, shape or configuration and/or knownrotational, translational and/or other functional and/or dynamicbehavior of the delivery cannula (e.g., flow rate, nozzle angle). Thevisualizations can include patient function data (e.g., fMRI data,electrical activity, active regions of a brain during a definedstimulation, fiber tracks, and the like).

The system can be configured to interrogate and segment image data tolocate fiducial markers in the image (e.g., an increased higherintensity pixel/voxel region and/or void created in the MRI image by thepresence of the delivery cannula in the patient's tissue) and generatesuccessive visualizations of the patient's anatomical structure and thedelivery cannula using MRI image data and a priori data of the deliverycannula to provide (substantially real-time) visualizations of thedistribution of the substance in the patient.

Some embodiments of the present invention can provide visualizations toallow more precise control, delivery, and/or feedback of an infusiontherapy so that the therapy or delivery cannula associated therewith canbe more precisely placed and/or so that the cannula or delivery can beadjusted to provide the desired distribution in tissue, or to confirmproper delivery and allow near real-time visualization of the procedure.

Some embodiments of the present invention are directed toreflux-resistant, MRI-compatible intrabody delivery cannulae.

Some embodiments of the present invention are directed to MRI-compatibleintrabody delivery cannulae including mechanisms that allow an operatorto selectively adjust a flow rate, port size, port number or othercomponents that adjust distribution of a substance delivered through thecannula to a target within the patient.

The delivery cannula may be used to precisely deliver any suitable anddesired substance (e.g., cellular, biological, and/or drug therapeutics)to the desired anatomy target. The delivery cannulae can be used in andthe systems can be configured to guide and/or place the delivery cannulain any desired internal region of the body of the patient, but may beparticularly suitable for neurosurgeries and delivery of a substance toa target area or region within the brain. The delivery cannulae andsystems can be used for gene and/or stem-cell based therapy delivery orother neural therapy delivery and allow user-defined custom targets inthe brain or to other locations. Cannulae, systems and methods of theinvention may be used to treat patients by delivery ofcellular/biological therapeutics into the desired anatomy to modifytheir cellular function. The cells (e.g., stem cells) may improvefunction.

The target region may be any suitable region or area within the patientbody. According to some embodiments, the target region is a STNanatomical region, which may be identified and located with reference tostandard anatomical landmarks. According to some embodiments, the targetarea is a deep brain tumor or other undesirable tissue mass.

According to some embodiments, the target is intrathecal. Theintrathecal target may be in the brain or spinal cord.

The substance delivered to the target region through the deliverycannula may be any suitable and desired substance. According to someembodiments, the substance is a liquid or slurry. In the case of atumor, the substance may be a chemotherapeutic (cytotoxic) fluid. Insome embodiments, the substance can include certain types ofadvantageous cells that act as vaccines or other medicaments (forexample, antigen presenting cells such as dentritic cells). Thedentritic cells may be pulsed with one or more antigens and/or with RNAencoding one or more antigen. Exemplary antigens are tumor-specific orpathogen-specific antigens. Examples of tumor-specific antigens include,but are not limited to, antigens from tumors such as renal cell tumors,melanoma, leukemia, myeloma, breast cancer, prostate cancer, ovariancancer, lung cancer and bladder cancer. Examples of pathogen-specificantigens include, but are not limited to, antigens specific for HIV orHCV. In some embodiments, the substance may comprise radioactivematerial such as radioactive seeds. Substances delivered to a targetarea may include, but are not limited to, the following as shown inTable 1:

TABLE 1 DRUG (generic name) DISORDER(S) caprylidene Alzheimer's diseasedonepezil Alzheimer's disease galantamine Alzheimer's disease memantineAlzheimer's disease Tacrine Alzheimer's disease vitamin E Alzheimer'sdisease ergoloid mesylates Alzheimer's disease riluzole Amyotrophiclateral sclerosis metoprolol Benign essential tremors primidone Benignessential tremors propanolol Benign essential tremors gabapentin Benignessential tremors & Epilepsy nadolol Benign essential tremors &Parkinson's disease zonisamide Benign essential tremors & Parkinson'sdisease carmustine Brain tumor lomustine Brain tumor methotrexate Braintumor cisplatin Brain tumor & Neuroblastoma ioversol Cerebralarteriography mannitol Cerebral Edema dexamethasone Cerebral Edema &Neurosarcoidosis baclofen Cerebral spasticity ticlopidine Cerebralthrombosis/embolism isoxsuprine Cerebrovascular insufficiency cefotaximeCNS infection & Meningitis acyclovir Encephalitis foscarnet Encephalitisganciclovir Encephalitis interferon alpha-2a Encephalitis carbamazepineEpilepsy clonazepam Epilepsy diazepam Epilepsy divalproex sodiumEpilepsy ethosuximide Epilepsy ethotoin Epilepsy felbamate Epilepsyfosphenytoin Epilepsy levetiracetam Epilepsy mephobarbital Epilepsyparamethadione Epilepsy phenytoin Epilepsy trimethadione Epilepsypregabalin Epilepsy & Neuralgia immune globulin Guillain-Barre Syndromeintravenous interferon beta-1b Guillain-Barre Syndrome & Multiplesclerosis azathioprine Guillain-Barre Syndrome & Multiple sclerosis &Neurosarcoidosis risperidone Head injury tetrabenazine Huntington'sdisease acetazolamide Hydrocephalus & Epilepsy alteplase Ischemic strokeclopidogrel Ischemic stroke nimodipine Ischemic stroke & Subarachnoidhemorrhage Aspirin Ischemic stroke & Thromboembolic stroke amikacinEncaphalitis ampicillin Encaphalitis ampicillin/sulbactam Encaphalitisceftazidime Encaphalitis ceftizoxime Encaphalitis cefuroximeEncaphalitis chloramphenicol Encaphalitis cilastatin/imipenemEncaphalitis gentamicin Encaphalitis meropenem Encaphalitismetronidazole Encaphalitis nafcillin Encaphalitis oxacillin Encaphalitispiperacillin Encaphalitis rifampin Encaphalitis sulfamethoxazole/Encaphalitis trimethoprim tobramycin Encaphalitis triamcinoloneEncaphalitis vancomycin Encaphalitis ceftriaxone Encaphalitis &Neurosyphilis pennicillin Encaphalitis & Neurosyphilis corticotropinMultiple sclerosis dalfampridine Multiple sclerosis glatiramer Multiplesclerosis mitoxantrone Multiple sclerosis natalizumab Multiple sclerosismodafinil Multiple sclerosis cyclophosphamide Multiple sclerosis & Braintumor & Neuroblastoma interferon beta-1a Multiple sclerosis & Neuritisprednisolone Multiple sclerosis & Neurosarcoidosis prednisone Multiplesclerosis & Neurosarcoidosis amantadine Multiple sclerosis & Parkinson'sdisease methylprednisolone Neuralgia desvenlafaxine Neuralgianortriptyline Neuralgia doxorubicin Neuroblastoma vincristineNeuroblastoma albendazole Neurocystecercosis chloroquine phosphateNeurosarcoidosis hydroxychloroquine Neurosarcoidosis infliximabNeurosarcoidosis pentoxyfilline Neurosarcoidosis thalidomideNeurosarcoidosis apomorphine Parkinson's disease belladonna Parkinson'sdisease benztropine Parkinson's disease biperiden Parkinson's diseasebromocriptine Parkinson's disease carbidopa Parkinson's diseasecarbidopa/entacapone/ Parkinson's disease levodopa carbidopa/levodopaParkinson's disease entacapone Parkinson's disease levodopa Parkinson'sdisease pergolide mesylate Parkinson's disease pramipexole Parkinson'sdisease procyclidine Parkinson's disease rasagiline Parkinson's diseaseropinirole Parkinson's disease rotiotine Parkinson's disease scopolamineParkinson's disease tolcapone Parkinson's disease trihexyphenidylParkinson's disease seleginline Parkinson's disease rivastigmineParkinson's disease & Alzheimer's disease anisindione Thromboembolicstroke warfarin Thromboembolic stroke 5-hydroxytryptophan Depression &Anxiety & ADHD duloxetine Depression & Anxiety & Bipolar disorderescitalopram Depression & Anxiety & Bipolar disorder venlafaxineDepression & Anxiety & Bipolar disorder & Autism & Social anxietydisorder desvenlafaxine Depression & Anxiety & PTSD & ADHD paroxetineDepression & Anxiety & PTSD & Social anxiety disorderfluoxetine/olanzapine Depression & Bipolar disorder 1-methylfolateDepression & BPD amitriptyline Depression & PTSD sertraline Depression &PTSD & Bipolar disorder & Social anxiety disorder fluvoxamine Depression& PTSD & Social anxiety disorder olanzapine Depression & Schizophrenia &Bipolar disorder paliperidone Depression & Schizophrenia & Bipolardisorder aripiprazole Depression & Schizophrenia & Bipolar disorder &Autism quetiapine Depression & Schizophrenia & PTSD & BPD & Bipolardisorder risperidone Depression & Schizophrenia & PTSD & BPD & Bipolardisorder & Autism amisulpride Depression & Social anxiety disorderchlorpromazine Psychosis droperidol Psychosis fluphenazine Psychosispericiazine Psychosis perphenazine Psychosis thiothixene Psychosistriflupromazine Psychosis haloperidol Psychosis & Dementia prazosin PTSDclozapine Schizophrenia flupenthixol Schizophrenia iloperidoneSchizophrenia loxapine Schizophrenia mesoridazine Schizophreniapromazine Schizophrenia reserpine Schizophrenia thioridazeinSchizophrenia zuclopenthixol Schizophrenia asenapine Schizophrenia &Bipolar disorder levomepromazine Schizophrenia & Bipolar disorderziprasidone Schizophrenia & Bipolar disorder molindone Schizophrenia &Psychosis pimozide Schizophrenia & Psychosis thioridazine Schizophrenia& Psychosis Cytarabine Chemotherapy, hematological malignancies

According to some embodiments, the surgical cannula is used to remove orwithdraw a substance therethrough from the target area. According tosome embodiments, the surgical cannula is used to remove cerebral spinalfluid from the patient.

Embodiments of the present invention may include steps, features,aspects, components, procedures and/or systems as disclosed in U.S.patent application Ser. No. 12/236,854, published as U.S. PublishedPatent Application No. 2009/071184, the disclosure of which isincorporated herein by reference.

According to some embodiments, the systems are configured to provide asubstantially automated or semi-automated and relatively easy-to-useMRI-guided system with defined workflow steps and interactivevisualizations. In particular embodiments, the systems define andpresent workflow with discrete steps for finding target and entrypoint(s), guiding the alignment of the targeting cannula to a plannedtrajectory, monitoring the insertion of the delivery cannula, andadjusting the (X-Y) position in cases where the placement needs to becorrected. During steps where specific MR scans are used, the circuit orcomputer module can display data for scan plane center and angulation tobe entered at the console. The workstation/circuit can passively oractively communicate with the MR scanner. The system can also beconfigured to use functional patient data (e.g., fiber tracks, fMRI andthe like) to help plan or refine a target surgical site and/or accesspath.

Embodiments of the present invention will now be described in furtherdetail below with reference to the figures. FIG. 1 illustrates anMRI-guided interventional system 10 with an MRI scanner 20, a clinicianworkstation 30 with at least one circuit 30 c, at least one display 32,an MRI compatible trajectory guide 50 t, a depth stop 70 (FIG. 5), and afluid substance delivery system 80. The fluid substance delivery systemincludes an MRI-compatible intrabody surgical or delivery cannula 100,an infusion pump 82 and connecting tubing 84. The system 10 can beconfigured to render or generate real time visualizations of the targetanatomical space using MRI image data and predefined data of at leastone surgical tool to segment the image data and place the trajectoryguide 50 t and the cannula 100 in the rendered visualization in thecorrect orientation and position in 3D space, anatomically registered toa patient. The trajectory guide 50 t and the cannula 100 can include orcooperate with tracking, monitoring and/or interventional components.

The tools of the system 10, including the cannula 100, can be providedas a sterile kit (typically as single-use disposable hardware) or inother groups or sub-groups or even individually, typically provided insuitable sterile packaging. The tools can also include a marking grid(e.g., as disclosed in U.S. Published Patent Application No.2009-00177077 and/or U.S. Published Patent Application No.2009/00171184). Certain components of the kit may be replaced or omitteddepending on the desired procedure. Certain components can be providedin duplicate for bilateral procedures.

With reference to FIG. 5, the depth stop 70 has a generally cylindricalconfiguration with opposite proximal and distal ends 70 a, 70 b and isadapted to be removably secured within the proximal end of the tubulartrajectory guide member 50 t. The depth stop 70 can be attached to thecannula 100 to allow for a defined insertion depth where insertion depthcontrol and/or locking, is desired.

The cannula 100 can be configured to flowably introduce and/or inject adesired therapy (e.g., antigen, gene therapy, chemotherapy or stem-cellor other therapy type). The cannula 100 as shown in FIG. 5 includes acannula body 110 defining at least one longitudinally extending lumen112, an inlet port 114 and at least one exit port 116. The cannula 100is formed of an MRI-compatible, MRI-visible material such as ceramic.The cannula 100 as depicted in FIG. 5 is a relatively simple embodimentand further embodiments including additional functionality will bedisclosed hereinbelow with reference to FIGS. 8-12E. These furtherembodiments of cannula may be used in the same manner as described withregard to the cannula 100.

The lumen 112 is fluidly connected to the pump 82 by the tubing 84. Thetubing 84 may be flexible tubing. According to some embodiments, thetubing 84 is PVC tubing. According to some embodiments, the tubing 84 issilicone tubing.

According to some embodiments and with reference to FIG. 3, the pump 82includes a reservoir 83 of the substance to be delivered and a pumpmechanism 81. The pump mechanism 81 is selectively operable to supplythe substance to the lumen 112 under a controlled pressure. According tosome embodiments, a syringe (e.g., a hand syringe) is used in place ofthe pump 82.

An exemplary trajectory guide 50 t is illustrated in FIGS. 1-3 inposition on a patient. As shown, the trajectory guide 50 t (FIG. 4)includes a guide frame 501, a targeting cannula 60 and trajectory guideactuators 51 having respective actuator cables 50 a (FIG. 2) (providingX-Y adjustment and pitch and roll adjustment) in communication with atrajectory adjustment controller 57. The frame 50 f can include acontrol arc 52 that cooperates with a platform 53 to provide pitch androll adjustments. The platform 53 can allow for X-Y adjustments of thetrajectory. The trajectory guide 50 t may include a plurality ofMRI-visible frame fiducial markers 50 fm around a base 50 b thereof. Foradditional discussion of suitable trajectory guides, see, U.S. PublishedPatent Application No. 2009-0112084, the contents of which are herebyincorporated by reference as if recited in full herein.

As shown in FIG. 5, the targeting cannula 60 includes an open centerlumen or through passage 61 along the axis of the targeting cannula 60.The distal end portion of the targeting cannula 60 can include afiducial marker 60 m (typically including a fluid-filled component 65),shown as a substantially spherical or round (cross-section) markershape. The proximal end 60 p can be configured with a fluid filledchannel 68 concentric with the passage 61 that can define a cylindricalfiducial marker. Other fiducial marker types can be used. The cannula100 can be slidably introduced and/or withdrawn through the lumen orpassage 61.

An MRI scanner interface 40 (FIG. 1) may be used to allow communicationbetween the workstation 30 and the scanner 20. The interface 40 and/orcircuit 30 c may be hardware, software or a combination of same. Theinterface 40 and/or circuit 30 c may reside partially or totally in thescanner 20, partially or totally in the workstation 30, or partially ortotally in a discrete device therebetween.

The MRI scanner 20 can include a console that has a “launch” applicationor portal for allowing communication to the circuit 30 c of theworkstation 30. The scanner console can acquire volumetric T1-weighted(post-contrast scan) data or other image data (e.g., high resolutionimage data for a specific volume) of a patient's head or other anatomy.In some embodiments, the console can push DICOM images or other suitableimage data to the workstation 30 and/or circuit 30 c. The workstation 30and/or circuit 30 c can be configured to passively wait for data to besent from the MR scanner 20 and the circuit 30 c/workstation 30 does notquery the scanner or initiate a communication to the scanner. In otherembodiments, a dynamic or active communication protocol between thecircuit 30 c/workstation 30 and the scanner 20 may be used to acquireimage data and initiate or request particular scans and/or scan volumes.Also, in some embodiments, pre-DICOM, but reconstructed image data, canbe sent to the circuit 30 c/workstation 30 for processing or display. Inother embodiments, pre-reconstruction image data (e.g., substantially“raw” image data) can be sent to the circuit 30 c/workstation 30 forFourier Transform and reconstruction.

Generally described, for some unilateral scenarios, the user (e.g.,doctor or surgeon) will proceed through a set of discrete workflow stepsto load MR image data, identify a target point, identify an entry point,verify the planned trajectory, and align the targeting cannula 60. Atarget point or region can also be planned or refined based on real-timefunctional image data of a patient. The functional image data caninclude, but is not limited to, images of fiber tracks, images ofactivity in brain regions during vocalization (e.g., reading, singing,talking), or based on physical or olfactory or sense-based stimulation,such as exposure to electrical (discomfort/shock input), heat and/orcold, light or dark, visual images, pictures or movies, chemicals,scents, taste, and sounds or the like) and/or using fMRI or otherimaging techniques. The enhanced visualization may give neurosurgeons amuch clearer picture of the spatial relationship of a patient's brainstructures. The visualizations can serve as a trajectory guide fordelivering a substance to the body (e.g., to the brain) via the surgical(intrabody) delivery cannula 100. In some embodiments, thevisualizations can be generated using data collated from different typesof brain-imaging methods, including conventional magnetic resonanceimaging (MRI), functional MRI (fMRI), diffusion-tensor imaging (DTI) andeven hyperpolarized noble gas MRI imaging. The MRI gives details on theanatomy, fMRI or other active stimulation-based imaging protocol canprovide information on the activated areas of the brain, and DTIprovides images of the network of nerve fibers connecting differentbrain areas. The fusion of one or all of these different images and thetool information can be used to produce a 3-D display with trajectoryinformation that surgeons can manipulate.

Thus, a target location and trajectory can be planned, confirmed orrefined based in-part on functional information of the patient. Thisfunctional information can be provided, in a user interface (UI)displayed on the display screen 32, in near real-time visualizations ofthe patient with the trajectory guide tools for trajectory path andtarget planning, e.g., visualize a patient's fiber track structuresand/or functional information of a patient's brain for a surgeon's easeof reference. Knowing where susceptible or sensitive brain regions areor where critical fiber tracks are in the patient's brain, can allow asurgeon to plan a better or less-intrusive trajectory and/or allow asurgeon to more precisely reach a desired target site and/or moreprecisely place a device and/or deliver a planned therapy substance.

To align the targeting cannula 60, scan volumes can be defined by thesystem based on known dimensions of the cannula, such as a cannulalength a position of a proximal or distal marker on the cannula, andangulation and lateral (X-Y) pivot limit.

An estimated distance from the distal tip of the cannula 100 to areference point on the guide frame 50 t (FIGS. 2 and 3) or the targetingcannula 60 (e.g., the proximal end of the targeting cannula 60) can bedetermined and physically or visually marked on the cannula 100. Thedepth stop 70 can be secured about the cannula 100 at the markedlocation. The depth stop 70 can serve to limit the depth of insertion ofthe cannula 100 into the patient in a subsequent insertion step orsteps.

The user can then (gradually) advance the cannula 100 and acquire images(on the display of the UI) to verify the trajectory and/or avoidfunctionally sensitive structure as appropriate. When the deliverycannula 100 has been advanced to the target point, high-resolutionconfirmation images can be obtained to verify the cannula tip locationrelative to the planned location. Additionally or alternatively,electrical activity can be sensed using an electrode at a tip of thecannula 100. If actual placement is not correct, the cannula 100 can bewithdrawn. At that point, either the X-Y placement can be adjustedappropriately (e.g., by moving a platform or stage an amount to causethe desired adjustment) or a trajectory angulation can be re-planned anda second attempt can be made.

For some bilateral scenarios, the above steps can be repeated for bothleft and right sides, with the additional goal that the patient shouldnot be moved into or out of the scanner. To satisfy that goal,trajectory planning should be completed for both sides prior to removingthe patient from the scanner. Also, burring and frame attachment (themember that holds the trajectory guide to the patient's head) should becompleted for both sides prior to moving the patient back into thescanner 20 to promote speed of the procedure.

The system 10 can be configured with a (hardware/software) interfacethat provides a network connection, e.g., a standard TCP/IP overEthernet network connection, to provide access to MR scanner 20, such asthe DICOM server. The workstation 30 can provide a DICOM C-STORE storageclass provider. The scanner console can be configured to be able to pushimages to the workstation 30 and the workstation 30 can be configured todirectly or indirectly receive DICOM MR image data pushed from an MRscanner console. Alternatively, as noted above, the system can beconfigured with an interface that allows for a dynamic and interactivecommunication with the scanner 20 and can obtain image data in otherformats and stages (e.g., pre-DICOM reconstructed or raw image data).

As noted above, the system 10 is configured so that hardware, e.g., thetrajectory guide 50 t and/or the cannula 100, constitute a point ofinterface with the system (software or computer programs) because thecircuit 30 c is configured with predefined tool data that recognizesphysical characteristics of specific tool hardware.

The system 10 may also include and implement a marking grid and/ornon-uniformly spaced-apart frame fiducial markers as disclosed in U.S.patent application Ser. No. 12/236,854, published as U.S. PublishedPatent Application No. 2009/00171184.

In some embodiments, circuit 30 c can be configured so that the programapplication can have distinct ordered workflow steps that are organizedinto logical groups based on major divisions in the clinical workflow asshown in Table 2. A user may return to previous workflow steps ifdesired. Subsequent workflow steps may be non-interactive if requisitesteps have not been completed. The major workflow groups and steps caninclude the following features or steps in the general workflow steps of“start”, “plan entry”, “plan target”, “navigate”, and “refine,”ultimately leading to delivering and visualizing the therapy (i.e.,delivering the substance to the target through the cannula 100) asdescribed in Table 2.

TABLE 2 Exemplary Clinical Workflow Groups/Steps Group Step DescriptionStart Start Set overall procedure parameters (Optionally confirmhardware compatibility) Plan Entry ACPC Acquire a volume and determineAC, PC, and MSP points Target Define initial target point(s) for entryplanning Trajectory Explore potential trajectories to determine entrypoint(s) Grid Locate physical entry point via fiducial grid. Plan ACPCWith hole burred and frame attached, acquire a Target volume anddetermine revised AC, PC, and MSP points. Target Acquire high-resolutionslabs (e.g., T2 slabs) to determine target positions in new volume.Trajectory Review final planned trajectory prior to starting procedure.Navigate Initiate Acquire slabs to locate initial position of cannula.Alignment Dynamically re-acquire scan showing position of top ofcannula. With each update show projected target position to determinewhen alignment is correct. Insertion Acquire slabs as cannula 100 isinserted into brain. Verify that cannula 100 is following plannedtrajectory. Refine Target Acquire images with cannula 100 in place.Review position and redefine target if necessary. Adjust XY Dynamicallyre-acquire scan showing position of Offset bottom of targeting cannula60. With each update show projected target position to determine whenoffset is correct. Insertion Acquire slabs as cannula 100 is insertedinto brain. Verify that cannula 100 is following planned trajectory.Delivery Substance Once cannula 100 position is finalized, prompt orDelivery user to begin delivery or withdrawal of With- substance throughcannula 100. drawal Watch Acquire slabs as substance is delivered intoor Diffusion withdrawn from brain and display. Delivery Pattern AdminAdmin Reporting and Archive functionality

The AC, PC and MSP locations can be identified in any suitable manner.In some embodiments, the AC-PC step can have an automatic, electronicAC, PC MSP Identification Library. The AC, PC and MSP anatomicallandmarks define an AC-PC coordinate system, e.g., a Talairach-Tournouxcoordination system that can be useful for surgical planning. Thislibrary can be used to automatically identify the location of thelandmarks. It can be provided as a dynamic linked library that a hostapplication can interface through a set of Application ProgrammingInterface (API) on Microsoft Windows®. This library can receive a stackof MR brain images and fully automatically locates the AC, PC and MSP.The success rate and accuracy can be optimized, and typically it takes afew seconds for the processing. The output is returned as 3D coordinatesfor AC and PC, and a third point that defines the MSP. This library ispurely computation and is typically UI-less. This library can fit aknown brain atlas to the MR brain dataset. The utility can be availablein form of a dynamic linked library that a host application caninterface through a set of Application Programming Interface (API) onMicrosoft Windows®. The input to this library can contain the MR braindataset and can communicate with applications or other servers thatinclude a brain atlas or include a brain atlas (e.g., have an integratedbrain atlas). The design can be independent of any particular atlas; butone suitable atlas is the Cerefy® atlas of brain anatomy (note:typically not included in the library). The library can be configured toperform segmentation of the brain and identify certain landmarks. Theatlas can then be fitted in 3D to the dataset based on piecewise affinetransformation. The output can be a list of vertices of the interestedstructures.

In some embodiments, the mid-sagittal plane (MSP) is approximated usingseveral extracted axial slices from the lower part of the input volume,e.g., about 15 equally spaced slices. A brightness equalization can beapplied to each slice and an edge mask from each slice can be createdusing a Canny algorithm. A symmetry axis can be found for each edge maskand identify the actual symmetry axis based on an iterative review andranking or scoring of tentative symmetry axes. The ranking/scoring cambe based on whether a point on the Canny mask, reflected through thesymmetry axis lands on the Canny mask (if so, this axes is scored forthat slice). An active appearance model (AAM) can be applied to a brainstem in a reformatted input stack with the defined MSP to identify theAC and PC points.

The MSP plane estimate can be refined as well as the AC and PC points.The MSP plane estimate can be refined using a cropped image with a smallregion that surrounds a portion of the brain ventricle and an edge maskusing a Canny algorithm. The symmetry axis on this edge mask if foundfollowing the procedure described above. The AC and PC points areestimated as noted above using the refined MSP and brightness peaks in asmall region (e.g., 6×6 mm) around the estimate are searched. Thelargest peak is the AC point. The PC point can be refined using the PCestimate above and the refined MSP. A Canny edge map of the MSP imagecan be computed. Again, a small region (e.g., about 6 mm×6 mm) can besearched for a point that lies on a Canny edge and for which the imagegradient is most nearly parallel to the AC-PC direction. The point ismoved about 1 mm along the AC-PC direction, towards PC. The largestintensity peak in the direction perpendicular to AC-PC is taken to bethe PC point.

It will be appreciated that when the target is a tumor or ventricle tobe infused or the like, the AC-PC points typically will not be used toprovide guidance.

The Navigation-Insertion step may include further aspects as describedin Table 3A:

TABLE 3A Navigate - Insertion Description The application can provide adepth value to set on the cannula 100 prior to insertion. Theapplication can prompt with scan parameters for oblique coronal andsagittal planes aligned to the trajectory. Also for an oblique axialperpendicular to the trajectory. On receiving coronal or sagittalimages, the application can display an overlay graphic indicating theplanned trajectory. The most recent coronal and sagittal images canappear together in a 1 × 2 display. On receiving a trajectory axial scanperpendicular to the trajectory, the application can segment out thecross-sections of the cannula 100 to determine the actual path beingfollowed by the cannula 100. On receiving a trajectory axial scanperpendicular to the trajectory, the application can display twoviewports containing: the axial stack with graphic overlays showing thedetected path of the cannula 100 on each image an anatomic axial viewthrough the target showing the planned target and the target projectedfrom the detected path of the cannula 100. An error value can show thedistance between the current projected target and the planned target. Ifmultiple trajectories have been defined for a single entry, theapplication can display the trajectory that is currently aligned duringinsertion.

The application may provide a depth value that is the expected distancefrom the target to the top of the targeting cannula 60. The operator canmeasure the depth value distance from the distal tip of the cannula 100and mark the proximal end point on the cannula 100 (e.g., with a sterilemarker). The depth stop 70 can then be secured at the marked locationand the measured insertion distance verified. The depth stop 70 isconfigured to limit a distance that the cannula 100 extends into thebody of a patient when the depth stop is inserted within the targetingcannula 60, so that full insertion of the cannula 100 up to the depthstop will provide the desired insertion depth.

In the event that the placement is not acceptable, the user may opt toproceed to the X-Y Adjustment workflow step as described in Table 3B:

TABLE 3B Refine-Adjust X-Y Offset Description The X-Y Adjustment stepcan display the current target and projected point as annotations to theimage data that was acquired during the Target Refinement step. Thisstep can prompt the user to acquire 2D images with scan plane parameterssuch that the image lies perpendicular to the trajectory and through thepivot point. On receiving a 2D image through the pivot point, the stepcan calculate the current projected target. This step can display linesfrom the current projected target to the revised target that indicatethe track the projected target would travel if the X and Y offset wheelswere turned independently. The lines can be colored to match colors onthe control wheels for X and Y offset respectively. A tool-tip (e.g.,pop-up) can provide text to describe the necessary action. (For example:“Turn X-offset knob to the Left”) This step can display an annotationindicating the location of the original planned target. When drawing thetarget and the current projection of the cannula path, the annotationscan be drawn to match the physical size of the cannula 100 diameter.

After the cannula 100 has been placed and the position has been acceptedby the user, the user may proceed to the substance delivery orwithdrawal step.

Again, it is noted that functional patient data can be obtained in nearreal-time and provided to the circuit 30 c/workstation 30 on the display32 with the visualizations of the patient anatomy to help in refining orplanning a trajectory and/or target location for placement of thecannula 100.

The system 10 can provide a UI to set target points so that thetrajectories through potential entry points can be investigated. Theuser may opt to overlay the outlines from a standard brain atlas overthe patient anatomy for comparison purposes which may be provided incolor with different colors for different structures. When using thebrain atlas, the user may opt to show either just the target structure(STN or GPi) or all structures. In either case, a tooltip (e.g., pop-up)can help the user to identify unfamiliar structures. The user may alsoopt to scale and/or shift the brain atlas relative to the patient imageto make a better match. To do this, the user may drag the white outlinesurrounding the brain atlas template. Fiber track structures and/orfunctional information of a patient's brain can be provided in avisually prominent manner (e.g., color coded or other visualpresentation) for a surgeon's ease of reference.

The UI can display images and information that enable the user to seehow well the cannula 100 is following the planned trajectory. The usermay opt to scan Axial, Coronal and Sagittal slabs along the cannula 100to visually determine the cannula 100 alignment in those planes. Theuser can also scan perpendicular to the cannula 100. In that case, thecircuit 30 c (e.g., software) can automatically identify where thecannula 100 is in the slab and it then shows a projection of the currentpath onto the target plane to indicate the degree and direction of errorif the current path is continued. The user can perform these scansmultiple times during the insertion. The automatic segmentation of thecannula 100 and the display of the projected target on the target planeprovide fully-automatic support for verifying the current path. TheCoronal/Sagittal views can provide the physician with a visualconfirmation of the cannula 100 path that does not depend on softwaresegmentation.

After completing the initial insertion of the cannula 100, the user(e.g., physician) may find that either the placement does not correspondsufficiently close or perfectly to the plan, or the plan was notcorrect. The UI can support functionality whereby the physician canwithdraw the cannula 100 and use the X and Y offset adjustments toobtain a parallel trajectory to a revised target. The UI can prompt theuser or otherwise acquire an image slab through the distal tip of thecannula 100. The UI can display the slab and on it the user may opt tomodify the target point to a new location or accept the current positionas final.

The UI can also support the user in adjusting a small X-Y offset to setthe targeting cannula 60 to a trajectory parallel to the original one.The UI can provide visualization of the position of the cannula 100 tiprelative to the target and with instructions on what physicaladjustments to make to obtain the desired parallel trajectory (shown as“turn Y wheel to the right”) and the projected error.

After the angular and/or X-Y adjustments are made, the cannula 100insertion is carried out in the same manner as described above.

After the cannula 100 has been inserted and had its position verified bythe physician, the UI can prompt the physician to begin delivery of thesubstance to the target via the cannula 100. In some embodiments, a testspray of a biocompatible fluid of similar density to the targettherapeutic substance (e.g., saline) may be first delivered to thetarget.

The physician (or other operator) then actuates the pump (or syringe) 82to begin driving a flow of the therapeutic substance through the tubing84 and the lumen 112 of the cannula 100. A mass flow of the substanceexits the cannula 100 through the exit port 116 into the target region Tor the vicinity of the target region T.

Using MRI image data, the system 10 may render or generate near realtime visualizations of the infused or delivered substance along with thenear real time visualizations of the target anatomical space and thecannula 100 in the UI. That is, in the same or similar manner to thesegmentation and visualization/display of the patient anatomy, theapplication can segment out the cross-sections of the deliveredsubstance to determine the actual volume occupied by the deliveredsubstance. Scans of scan planes proximate the distal tip of the cannula100 or associated with target regions can be acquired. The MR image datacan be obtained and the actual distribution of the delivered substancein tissue can be shown on the display. These visualizations can bedynamically rendered (e.g., in near real time) to show the dynamicdispersion and/or infusion pattern and/or path of the infused substance.In some embodiments, an MR contrast agent or fluid can be provided inthe delivered substance having an increased SNR relative to the tissue.

FIG. 6A illustrates a screen shot from the UI that allows the user tosee the distribution of the delivered substance, which is represented inthe UI by the displayed image A. This screen shot illustrates coronaland sagittal views to the target (e.g., STN). The user may opt to scanCoronal and Sagittal slabs along the cannula 100 to visually determinethe distribution pattern or flow paths in those planes. The user canalso scan perpendicular to the cannula 100. The cannula 100 isrepresented in the screen shot by an image 100′ and the targetingcannula 60 is represented in the screen shot by an image 60′. FIG. 6Billustrates an axial slab through the target T. The user can performthese scans multiple times during delivery of the substance. Theautomatic segmentation and display of the delivered substance, thepatient anatomy and the cannula 100 provide fully-automatic support forverifying or assessing the anatomical flow paths, diffusion, dispersion,permeation and/or other distribution of the delivered substance in thepatient.

The delivered substance may be visually highlighted in the display ofthe UI. For example, a graphical overlay or outline H may be provided inone or more of the displayed views that highlights the image of thedelivered substance A. By way of further example, the image of thedelivered substance A in the tissue may be provided with a contrastingcoloring or shading.

As noted above, the operator can perform scans multiple times during theprocedure to track or assess the delivery performance. The UI may allowthe operator to display the MR image data in a manner that assists theoperator in comparing the flow and/or distribution of the deliveredsubstance over time. FIG. 6C illustrates a screen shot from the UIincluding a view V1 including an image A of the delivered substance at afirst time (e.g., “t=5 minutes”) and a view V2 including an image A ofthe delivered substance A at a second, subsequent time (e.g., “t=10minutes”). The UI may also display (e.g., in a view V3) relevant datasuch as the pump settings, flow rate, delivery cannula port settings,and/or nozzle angle at each of the selected times or any interveningadjustments. The UI may also display indicia F, such as graphical arrowsindicating the directions of flow or dispersion, for example, betweenthe selected times or over time. The foregoing visualization aids mayassist the operator in assessing the effect of adjustments in flowrates, delivery cannula placement, or delivery cannula settings, forexample.

FIG. 7A illustrates a screen shot from the UI in the case where thetarget region is a tumor site in a patient's brain. The tumor site issegmented and displayed as a part of the patient anatomy and the image Cof the tumor may be highlighted, enhanced, contrasted or otherwiseaugmented to enable the operator to more easily discern the tumor imageC in the displayed image. The UI enables the user to see thedistribution of the infused substance with respect to the tumor site.This screen shot illustrates coronal and sagittal views through thetumor. The user may opt to scan Coronal and Sagittal slabs along thecannula 100 to visually determine the distribution pattern or flow pathsin those planes. The user can also scan perpendicular to the cannula100. FIG. 7B illustrates an axial slab through the tumor. The user canperform these scans multiple times during delivery of the substance. Theautomatic segmentation and display of the infused substance, the patientanatomy (including the tumor) and the cannula 100 providefully-automatic support for verifying or assessing the anatomical flowpaths, diffusion, dispersion and distribution of the infused substancewith respect to the tumor site and the remainder of the patient anatomy.

The operator can use the feedback from the UI to assess, re-plan and/ormodify the infusion procedure.

Responsive to the UI feedback, the operator may adjust one or moreoperational parameters during the fluid delivery. For example, the massflow rate of the substance exiting the cannula 100 can be increased ordecreased. This may be accomplished by adjusting the mass flow ratesetting of the infusion pump 82 or a regulator (e.g., restrictor orvalve) upstream of the cannula 100. In some cases (e.g., as describedbelow with reference to FIG. 10), the delivery cannula includes a flowcontrol mechanism that can be used to adjust the mass flow rate ofinfusion.

The operator may adjust the placement of the exit port responsive to theUI feedback. For example, the operator may insert the cannula 100further into the patient or withdraw the end of the cannula 100 somewhatfrom the patient. The operator may fully withdraw the cannula 100 fromthe patient, plan a new target and trajectory, re-insert the cannula 100to the new target, and re-initiate delivery of the substance to the newtarget through the cannula 100. This procedure may be used one or moretimes in order to infuse the substance into different regions of atumor, for example. Different cannulas or a protective (e.g.,retractable) sheath may be used to inhibit spread of tumor cells.

The operator may adjust the delivery flow pattern of the substanceexiting from the delivery cannula responsive to the UI feedback. Thismay be accomplished using a mechanism or mechanisms of a deliverycannula suitably modified to enable flow pattern modification. Accordingto some embodiments (e.g., as described below with reference to FIGS.9A-11), the cannula 200, 300, 400, 500 is configured to allow theoperator to modify the delivery flow pattern in situ (i.e., while thedelivery cannula is situated in the target region). The adjustmentmechanism(s) may include a mechanism to adjust a size of an exit port,to adjust the number of open ports for substance egress, and/or toadjust (e.g., axially or circumferentially) the location of one or moreopen exit ports to adjust the nozzle angle and the like. These cannulaecan have any other features described herein although not specificallydiscussed or shown.

With reference to FIG. 8, one exemplary MRI-compatible intrabodysurgical cannula (e.g., delivery cannula) 200 according to embodimentsof the present invention is shown therein. It is noted that exemplaryembodiments of the surgical cannula described herein can be used asdescribed above with respect to the cannula 100. Also one or morefeatures from one or more embodiments can be combined or used in otherembodiments. The surgical cannula 200 includes a tubular outer sleeve220 and a tubular inner sleeve 230 axially slidably mounted in the outersleeve 220. The inner sleeve 230 defines a central lumen 232 and an exitport 234. In use, the inner sleeve 230 can be telescopingly extended andretracted relative to the outer sleeve 220 to selectively adjust theeffective length of the surgical cannula 200 and the position of theexit port 234 with respect to the target region. The outer sleeve 220can also act as a protective sheath that encases the inner sleeve 230until the cannula tip reaches tissue proximate the tumor site, at whichtime the inner sleeve 230 can be extended. At withdrawal of the cannula200, the inner sleeve 230 can be withdrawn or retracted into the outersleeve 220 so as not to expose healthy tissue to tumor cells.

With reference to FIGS. 9A and 9B, an alternative MRI-compatibleintrabody surgical cannula (e.g., delivery cannula) 300 according toembodiments of the present invention is shown therein and may be used inplace of the cannula 100. The surgical cannula 300 includes a tubularouter sleeve 320 and a tubular inner sleeve 330 slidably mounted in theouter sleeve 320 to permit relative rotation between the sleeves 320,330. The inner sleeve 330 defines a central lumen 332 and an exit port334. The outer sleeve 320 defines four circumferentially spaced apartexit ports 324 a, 324 b, 324 c, 324 d. In use, the inner and outersleeves 320, 330 can be relatively rotated to align the exit port 334,alternatively, with each of the exits ports 324 a, 324 b, 324 c, 324 d.In this way, the operator can selectively deliver the substance througha chosen side exit port 324 a, 324 b, 324 c, 324 d in each of fourlateral directions. The side exit ports 324 a, 324 b, 324 c, 324 d canalso be axially offset.

With reference to FIG. 10, an alternative MRI-compatible intrabodysurgical cannula (e.g., delivery cannula) 400 according to embodimentsof the present invention is shown therein and may be used in place ofthe cannula 100. The surgical cannula 400 includes a tubular outersleeve 420 and a tubular inner sleeve 430 slidably mounted in the outersleeve 420 to permit relative rotation between the sleeves 420, 430. Theinner sleeve 430 defines a central lumen 432 and an exit port 434. Theouter sleeve 420 defines an exit port 424. In use, the inner and outersleeves 420, 430 can be relatively rotated to align the exit ports 424,434 with differing amounts of overlap. By selectively adjusting theoverlap between the exit ports 424, 434, the size of the effective exitport 435, and thereby the mass flow rate of delivery, can be adjusted.

With reference to FIG. 11, an alternative MRI-compatible intrabodysurgical cannula (e.g., delivery cannula) 500 according to embodimentsof the present invention is shown therein and may be used in place ofthe cannula 100. The surgical cannula 500 includes a tubular outersleeve 520 and a tubular inner sleeve 530 slidably mounted in the outersleeve 520 to permit relative rotation between the sleeves 520, 530. Theinner sleeve 530 defines a central lumen 532 and a helical exit slot534. The outer sleeve 520 defines a helical exit slot 524. The area ofintersection or overlap B between the exit slots 524, 534 defines aneffective exit port 535. In use, the outer and inner sleeves 520, 530can be selectively relatively rotated to change the location of the areaof intersection B and thereby the axial position of the exit port 535along the length of the surgical cannula 500.

In the case of a surgical cannula having side ports (e.g., the cannulae300, 400, 500), the terminal end of the lumen may be closed so thatthere is no exit port corresponding to the exit port 116 (FIG. 5).According to some embodiments, an endwise exit port corresponding to theexit port 116 is provided, but a mechanism is provided to selectivelyclose the endwise exit port (e.g., when a “side firing” exit port 324 a,435, 535 is opened).

In the case of surgical cannulae such as the surgical cannulae of FIGS.9A-11 having relatively movable sleeves or other components, featuresmay be provided to allow tracking or determine the relative positions ofthe components (e.g., the inner and outer sleeves). In particular, itmay be desirable to enable such assessment while the delivery surgicalremains in situ. Exemplary mechanisms are discussed hereinbelow withreference to FIGS. 9A, 9B and 11; however, it will be appreciated thatthe several different mechanisms can be used on surgical cannula ofdifferent designs than those with which they are depicted.

As discussed herein, properties of the surgical cannula may bepredefined or known a priori to the circuit 30 c or the operator. Suchproperties may include the size and geometry of the surgical cannula aswell as the available cannula component settings or relationshipsaffecting or determining functional characteristics of the surgicalcannula with respect to substance flow. The available component settingsor relationships may include the ranges of motion between cannulacomponents (e.g., between the inner and out sleeves) and the alternativecannula configurations resulting from different relative positions ofthe components. The variable functional characteristics may include thesize, number, shape, nozzle angle or direction, axial position along thecannula, and/or circumferential position of the exit port(s) of each ofthe inner and outer sleeves or of the effective exit ports(s).

Using this knowledge of the characteristics of the surgical cannula incombination with determination of the present positions of the pertinentcannula components with respect to one another and/or with respect tothe patient anatomy, the circuit 30 c or operator can make suitablemodifications to the surgical cannula in situ to reconfigure thesurgical cannula to new settings (and, in some cases, reposition thedelivery cannula with respect to the patient anatomy) and thereby modifyone or more of the aforementioned functional characteristics.

By way of example, a delivery cannula may be inserted as describedherein and delivery of the substance may be begun. The operator,referring to the displayed visualization of the patient or in accordancewith a prescribed protocol, may wish to subsequently revise the settingsto deliver the substance from the same general location but in adifferent radial direction. The operator can obtain the desired newsettings by adjusting or manipulating the delivery cannula in accordancewith the pre-known characteristics of the delivery cannula and thecurrent position/configuration of the delivery cannula as determinedfrom the MR image data. Likewise, in some embodiments, the circuit 30 ccan programmatically evaluate the MR data to determine the currentposition/configuration of the delivery cannula, determine theadjustments needed to achieve a desired new cannula configuration toprovide a corresponding new substance flow pattern or flow rate, andreport the necessary adjustments to the operator. The adjustments may beadjustments of the components relative to one another (e.g., rotatingthe inner sleeve 430 relative to the outer sleeve 420 to adjust the sizeof the effective exit port 435) and/or relative to the patient (e.g.,rotating the outer sleeve 420 relative to the target to adjust the angleor direction of flow from the effective exit port 435). Methods andapparatus as described can thus provide for improved or preciseadjustment and control over the location and characteristics (e.g.,direction and flow rate) of the flow of the substance dispensed from thedelivery cannula.

According to some embodiments and with reference again to FIG. 11,MRI-visible marks M1, M2 or fiducial markers are mounted on the outersleeve 520 and the inner sleeve 530, respectively. The MRI-visible markM1 travels with the sleeve 520 and the MRI-visible mark M2 travels withthe sleeve 530. The marks M1, M2 each appear in the MR image asdisplayed on the UI so that the operator can observe their relativerotational positions and thereby determine the location or pattern ofthe effective exit port 535. A look up chart or the like may be providedto assist the operator in this determination.

Alternatively, the MRI-visible marks M1, M2 may be scanned and processedby the circuit 30 c. The system 10 may programmatically determine thecorresponding exit port configuration and report the same to theoperator via the UI. Alternatively, the operator can select a desireddelivery flow rate and/or flow pattern and the system canprogrammatically correlate the substance to the position of the sleevesand instruct the operator as to the rotation required.

According to some embodiments and with reference again to FIG. 9B, anelectronic position sensor device 72 is mounted on the surgical cannula300. The electronic position sensor device 72 may include an encoder,for example, that generates digital pulses to the circuit 30 ccorresponding to the relative rotational positions of the sleeves 320,330. The system 10 may programmatically determine the corresponding exitport configuration and report the same to the operator via the UI.

With reference to FIGS. 12A-12E, a cannula system 601 according toembodiments of the present invention is shown therein. The system 601includes an MRI-compatible intrabody surgical (e.g., delivery) cannula600 (hereinafter, the delivery cannula 600) particularly well-suited fordelivering a substance to a patient, connecting tubing 660, and a luerfitting (e.g., luer lock) 652. The system 601 may be used in place ofthe cannula 100 and the connecting tubing 84.

The cannula 600 includes a rigid tubular support sleeve 610. The supportsleeve 610 defines an axially extending central lumen 612. An exitopening 614 on the distal end of the support sleeve 610 and an inletopening 616 on the proximal end of the support sleeve 610 each fluidlycommunicate with the lumen 612. The outer surface 618 of the supportsleeve 610 includes a proximal section 618A having a substantiallyuniform diameter D8. The outer surface 618 also includes a distalsection 618B having a tapered or frusto-conical shape that tapers in theaxial distal direction. The outer surface 618 further includes distalend face 618C.

According to some embodiments, the support sleeve 610 is formed of asubstantially rigid MRI-compatible material. According to someembodiments, the support sleeve 610 is formed of an MR safe material.According to some embodiments, the MRI-compatible material is a ceramic.Suitable ceramics may include Alumina. Other MRI-compatible materialsthat may be used for the sleeve 610 may include glass or rigid polymers.

A conformal outer polymeric sleeve 640 surrounds and fits tightly aboutthe support sleeve 610. According to some embodiments, the polymericsleeve 640 is formed of polyethylene terephthalate (PET). According tosome limits, the polymeric sleeve 640 is an elastomeric shrinkablesleeve.

The inner sleeve 620 extends through the lumen 612. The inner sleeve 620is secured to the inner surface of the support sleeve 610. According tosome embodiments, the inner sleeve 620 is bonded to the inner surface ofthe support sleeve 610 by a layer of adhesive G1 such as LOCTITE® 4014adhesive.

The inner sleeve 620 defines an axially extending central lumen 622. Anexit opening 624 on the distal end of the inner sleeve 620 and an inletopening 626 on the proximal end of the inner sleeve 620 each fluidlycommunicate with the lumen 622. An extension section 620A of the innersleeve 620 extends beyond the distal end of the support sleeve 610 andis exposed. The distal end of the inner sleeve 620 defines a distal endface 620B. A proximal extension section 620C of the inner sleeve 620extends beyond the proximal end of the support sleeve 610 and throughthe connecting tubing 660 to an infusion pump, for example.

According to some embodiments, the inner sleeve 620 is formed of asubstantially rigid MRI-compatible material. According to someembodiments, the MRI-compatible material is fused silica.

A transfer tube 630 extends through the lumen 622. The transfer tube 630is secured to the inner surface of the inner sleeve 620. According tosome embodiments, the transfer tube 630 is bonded to the inner surfaceof the inner sleeve 620 by a layer of adhesive G2, such as LOCTITE® 4014adhesive.

The transfer tube 630 defines an axially extending central lumen 632. Anexit opening 634 on the distal end of the transfer tube 630 and an inletopening 636 on the proximal end of the transfer tube 630 each fluidlycommunicate with the lumen 632. A distal extension section 630A of thetransfer tube 630 extends beyond the distal end of the inner sleeve 620and is exposed. A proximal extension section 630C (FIG. 12C) of thetransfer tube 630 extends beyond the proximal end of the support sleeve610 and through the connecting tubing 660 to an infusion pump, forexample.

According to some embodiments, the transfer tube 630 is formed of asubstantially rigid MRI-compatible material. According to someembodiments, the MRI-compatible material is fused silica.

The connecting tubing 660 (FIGS. 12B, 12C and 12D) is coupled to theproximal end of the support sleeve 610 by a tubing adapter 662. Thetubing adapter 662 may be bonded to the support sleeve 610 and theconnecting tubing 660 by an adhesive G3, such as LOCTITE™ UV 3311adhesive. The connecting tubing 660 may be formed of any suitable MRIcompatible material. According to some embodiments, the connectingtubing 660 is formed of polyvinyl chloride (PVC). According to someembodiments, the connecting tubing 660 is formed of silicone. The tubingadapter 662 may be formed of any suitable MRI compatible material, suchas an MRI-compatible polymer.

The luer fitting 652 is coupled to the proximal end of the connectingtubing 660 by a luer adapter 654. The luer adapter 654 may be bonded tothe luer fitting 652 and the connecting tubing 660 by an adhesive G4,such as LOCTITE™ UV 3311 adhesive. The luer adapter 654 may be formed ofany suitable MRI compatible material, such as an MM-compatible polymer.The luer fitting 652 may also be bonded to the inner sleeve 620 by oneor more the adhesives G5, G6, such as LOCTITE® UV 3311 adhesive and/orLOCTITE® UV 4014 adhesive.

According to some embodiments, the inner diameter D1 of the transfertube 630 is in the range of from about 10 μm to 1 mm and, in someembodiments, is about 200 μm. According to some embodiments, the outerdiameter D2 of the transfer tube 630 is in the range of from about 75 μmto 1.08 mm and, in some embodiments is about 360 μm. According to someembodiments, the length L1 of the exposed section 630A of the transfertube 630 is in the range of from about 1 mm to 50 mm and, in someembodiments is about 3 mm.

According to some embodiments, the inner diameter D4 of the inner sleeve620 is in the range of from about 85 μm to 1.1 mm and, in someembodiments, is about 450 μm. According to some embodiments, the outerdiameter D5 of the inner sleeve 620 is in the range of from about 150 μmto 1.5 mm and, in some embodiments, is about 673 μm. According to someembodiments, the length L4 of the exposed section 620A of the innersleeve 620 is in the range of from about 1 mm to 75 mm and, in someembodiments is about 15 mm.

According to some embodiments, the inner diameter D7 of the supportsleeve 610 is in the range of from about 160 μm to 1.55 mm and, in someembodiments, is about 750 μm. According to some embodiments, the outerdiameter D8 of the uniform diameter section 618A of the support sleeve610 is in the range of from about 500 μm to 4 mm and, in someembodiments, is about 1.6 μm. According to some embodiments, the overalllength L7 of the support sleeve 610 is in the range of from about 0.5inch to 20 inches and, in some embodiments, is in the range of fromabout 10 to 14 inches. According to some embodiments, the length L8 ofthe tapered section 618B of the support sleeve 610 is in the range offrom about 6 to 9 mm.

According to some embodiments, the thickness of the conformal polymericsleeve 640 is in the range of from about 40 to 60 μm. According to someembodiments, the length of the conformal polymeric sleeve 640 issubstantially coextensive with the support sleeve 610.

As best seen in FIG. 12E, the cannula 600 is a stepped cannula withthree co-axially disposed step segments (the outer surfaces of thetransfer tube 630, the inner sleeve 620 and the conformal polymericsleeve 640, respectively) having different outer diameters and separatedby the steps or rises of the end faces 618C, 620B.

The cannula 600 may be a unitary, integral structure having norelatively slidably elements.

The cannula 600 may be used in the same manner as described herein withrespect to the cannula 100, for example. The luer can be operativelycoupled to an infusion pump (e.g., the infusion pump 82) or syringe,which supplies a mass flow of the desired substance or material to bedelivered into the patient.

The cannula 600 can provide a number of advantages. The rigid supportsleeve 610 prevents or inhibits bending or flex of the large majority ofthe length of the cannula 600 as the cannula 600 is inserted through thetargeting cannula 60 and into the patient (e.g., the brain). Byrestricting the axial movement of the cannula 600 during insertion, thecannula 600 can reduce or prevent small movements that may disrupttissue and thereby lead to reflux of the infused substance. A ceramicsupport sleeve 610, in particular, can provide good rigidity while alsobeing MRI-compatible and MRI safe. According to some embodiments, theentirety of the cannula 600 is formed of an MRI-compatible, MR safematerial or materials.

The conformal polymeric sleeve 640 may beneficially provide a lubricioussurface over the support sleeve 610 to reduce shear force on the brainor other tissue during insertion. The conformal polymeric sleeve 640 canenhance the safety of the cannula 600 by capturing the support sleeve610 or pieces thereof if the support sleeve is accidentally broken insitu.

The steps S1, S2 and the end faces 618C, 620B can serve to reduce orprevent reflux of the delivered substance. The provision of an exposedtransfer tube section 630A having the aforedescribed length L1 and innerdiameter D1 has also been found to provide beneficial reflux resistanceperformance.

The tapered transition 618B between the outer diameter D5 of the innersleeve 620 and the outer diameter D8 of the support sleeve 610 canprovide the reflux control of the small diameter inner sleeve 620 alongwith a support sleeve 610 having a geometry providing satisfactoryrigidity and size for cooperation with the targeting cannula 60 oradapter 74.

The protective connecting tubing 660 can serve to protect the transfertube 630 while also permitting convenient routing the connecting tubing660 to the infusion pump. According to some embodiments, the length L11of the tubing 660 is in the range of from about 6 to 12 feet.

According to some embodiments, the infusate is delivered to a patient'sbrain through the exit opening 634 at an infusion rate in the range offrom about 1 to 3 μL/minute.

As discussed herein, insertion of the surgical cannula 100 (or any othersurgical, e.g., delivery, cannula) can be tracked in near real time byreference to a void in the patient tissue caused by the cannula 100 andreflected in the MR image. In some embodiments, one or more MRI-visiblefiducial markers may be provided on the surgical cannula 100, MR scannedand processed, and displayed on the UI. In some embodiments, thesurgical cannula 100 may itself be formed of an MRI-visible material, MRscanned and processed, and displayed on the UI.

According to some embodiments, the surgical cannula may include anembedded intrabody MRI antenna that is configured to pick-up MRI signalsin local tissue during an MRI procedure. The MRI antenna can beconfigured to reside on a distal end portion of the surgical cannula. Insome embodiments, the antenna has a focal length or signal-receivinglength of between about 1-5 cm, and typically is configured to have aviewing length to receive MRI signals from local tissue of between about1-2.5 cm. The MRI antenna can be formed as comprising a coaxial and/ortriaxial antenna. However, other antenna configurations can be used,such as, for example, a whip antenna, a coil antenna, a looplessantenna, and/or a looped antenna. See, e.g., U.S. Pat. Nos. 5,699,801;5,928,145; 6,263,229; 6,606,513; 6,628,980; 6,284,971; 6,675,033; and6,701,176, the contents of which are hereby incorporated by reference asif recited in full herein. See also U.S. Patent Application PublicationNos. 2003/0050557; 2004/0046557; and 2003/0028095, the contents of whichare also hereby incorporated by reference as if recited in full herein.

According to some embodiments and with reference to FIG. 13, an adaptersleeve 74 is provided to take up the radial gap between the innerdiameter of the targeting cannula 60 and the outer diameter of anMRI-compatible surgical cannula 700.

Surgical cannulae 100-700 as described herein may be used with astereotactic frame or without a stereotactic frame.

While the surgical cannulae 100-700 have been identified herein asdelivery cannulae and methods for delivering a substance to a patienthave been described, in accordance with some embodiments of theinvention, the surgical cannulae and methods can be used to withdraw asubstance (e.g., spinal fluid) from a patient. Thus, it will beappreciated that surgical cannulae and methods as disclosed herein canbe used to transfer a substance into and/or from a patient.

While the surgical cannulae 100-700 have been described herein withreference to MRI-guided insertion and infusion procedures, in someembodiments the cannulae can be used in procedures without MRI guidance.

While the surgical cannulae 100-700 have been described in use with atrajectory guide 50 b, the cannulae may be used with other types oftrajectory guidance or stereotactic frames or without a stereotacticframe or trajectory guide.

The surgical cannulae 100-700 as depicted in FIGS. 1-13 would typicallybe employed for acute treatments. However, the systems, cannulae,methods and procedures described herein may likewise be used forinstallation of a chronic delivery cannula or catheter. An exemplarychronic substance delivery system 880 is shown in FIG. 14. The system880 includes a delivery cannula 800, a port device 886, connectiontubing 884 and an infusion pump 882. The system 880 may be installed inthe same manner as the system 80 (FIG. 1) except that the deliverycannula 800 is configured to remain in the patient post-first deliveryand the port device 886 is installed on the patient (e.g., behind thepatient's ear) to provide an (external) access point for subsequentlyreleasably coupling the connection tubing 884 to the delivery cannula800. The pump 882 can be periodically or continuously connected to thedelivery cannula 800 to deliver a therapeutic substance to a targetregion of the patient through the delivery cannula 800. In someembodiments, the connecting tubing, the pump and substance reservoir maybe implanted in the patient and connected to the delivery cannula 800 bythe tubing so that the port device 886 is not needed, similar to an IPGand electrical stimulation lead. The chronic system can allow deliveryof the substance or substances at different delivery times withoutrequiring another surgical implantation procedure to place the deliverycannula. FIG. 14B illustrates the delivery cannula 800 and the portdevice 886 with the connection tubing 884 and the pump 882 disconnectedand the port device 886 closed to cap the access path to the deliverycannula 800.

According to some embodiments, the substance delivered via the deliverycannula includes radioactive objects such as radioactive seeds. In thisevent, the delivery cannula may include a suitable radiation shield orshielding material in order to reduce or prevent the exposure of tissueoutside the target region to radiation from the radioactive objects.

The system 10 may also include a decoupling/tuning circuit that allowsthe system to cooperate with an MRI scanner 20 and filters and the like.See, e.g., U.S. Pat. Nos. 6,701,176; 6,904,307 and U.S. PatentApplication Publication No. 2003/0050557, the contents of which arehereby incorporated by reference as if recited in full herein.

The system 10 can include circuits and/modules that can comprisecomputer program code used to automatically or semi-automatically carryout operations to generate visualizations and provide output to a userto facilitate MRI-guided diagnostic and therapy procedures. FIG. 15 is aschematic illustration of a circuit or data processing system that canbe used with the system 10. The circuits and/or data processing systemsmay be incorporated in one or more digital signal processors in anysuitable device or devices. The processor 90 communicates with an MRIscanner 20 and with memory 94 via an address/data bus 92. The processor90 can be any commercially available or custom microprocessor. Thememory 94 is representative of the overall hierarchy of memory devicescontaining the software and data used to implement the functionality ofthe data processing system. The memory 94 can include, but is notlimited to, the following types of devices: cache, ROM, PROM, EPROM,EEPROM, flash memory, SRAM, and DRAM.

The memory 94 may include several categories of software and data usedin the data processing system: the operating system 94A; the applicationprograms 94C; the input/output (I/O) device drivers 94B; and data 94F.The data 94F can also include predefined characteristics of differentsurgical tools and patient image data 94G. The application programs 94Ccan include a Near Real-Time Substance Dispersion Visualization Module94D, Interventional Tool Data Module 94E, a Tool Segmentation Module 94H(such as segmentation modules for a targeting cannula, a trajectoryguide frame and/or base, and a delivery cannula), and a workflow groupUser Interface Module 94I (that facilitates user actions and providesguidance to obtain a desired trajectory or a desired drug dispersionpattern, such as physical adjustments to achieve same).

As will be appreciated by those of skill in the art, the operatingsystems 94A may be any operating system suitable for use with a dataprocessing system, such as OS/2, AIX, DOS, OS/390 or System390 fromInternational Business Machines Corporation, Armonk, N.Y., Windows CE,Windows NT, Windows95, Windows98, Windows2000 or other Windows versionsfrom Microsoft Corporation, Redmond, Wash., Unix or Linux or FreeBSD,Palm OS from Palm, Inc., Mac OS from Apple Computer, LabView, orproprietary operating systems. The I/O device drivers 94C typicallyinclude software routines accessed through the operating system 94A bythe application programs 94C to communicate with devices such as I/Odata port(s), data storage 94F and certain memory 94 components. Theapplication programs 94C are illustrative of the programs that implementthe various features of the data processing system and can include atleast one application, which supports operations according toembodiments of the present invention. Finally, the data 94F representsthe static and dynamic data used by the application programs 94C, theoperating system 94A, the I/O device drivers 94C, and other softwareprograms that may reside in the memory 94.

While the present invention is illustrated, for example, with referenceto the Modules 94C, 94D, 94E, 94H, 94I being application programs inFIG. 15, as will be appreciated by those of skill in the art, otherconfigurations may also be utilized while still benefiting from theteachings of the present invention. For example, the Modules 94C, 94D,94E, 94H, 94I and/or may also be incorporated into the operating system94A, the I/O device drivers 94B or other such logical division of thedata processing system. Thus, the present invention should not beconstrued as limited to the configuration of FIG. 15, which is intendedto encompass any configuration capable of carrying out the operationsdescribed herein. Further, one or more of modules, i.e., Modules 94C,94D, 94E, 94H, 94I can communicate with or be incorporated totally orpartially in other components, such as a workstation, an MRI scanner, aninterface device. Typically, the workstation 30 will include the modules94C, 94D, 94E, 94H, 94I and the MR scanner with include a module thatcommunicates with the workstation 30 and can push image data thereto.

The I/O data port can be used to transfer information between the dataprocessing system, the circuit 30 c or workstation 30, the MRI scanner20, and another computer system or a network (e.g., the Internet) or toother devices controlled by or in communication with the processor.These components may be conventional components such as those used inmany conventional data processing systems, which may be configured inaccordance with the present invention to operate as described herein.

It is noted that any one or more aspects or features described withrespect to one embodiment, may be incorporated in a different embodimentalthough not specifically described relative thereto. That is, allembodiments and/or features of any embodiment can be combined in any wayand/or combination. Applicant reserves the right to change anyoriginally filed claim or file any new claim accordingly, including theright to be able to amend any originally filed claim to depend fromand/or incorporate any feature of any other claim although notoriginally claimed in that manner. These and other objects and/oraspects of the present invention are explained in detail in thespecification set forth below.

FIG. 16 is an exemplary screen shot of a display of a user interfacefrom an actual MRI-guided infusion procedure on a (monkey) brain usingan intrabody cannula generally corresponding to the cannula 600. Thescreen shot includes an image (i.e., the white portions at the top ofthe screen) of the targeting cannula 60, and an image (i.e., the whiteportion in the brain region) of the infused substance in the brain.

FIGS. 17A and 17B are further exemplary screen shots of a display of auser interface from an actual MRI-guided infusion procedure on a(monkey) brain using an intrabody cannula generally corresponding to thecannula 600. The screen shots of FIGS. 17A and 17B each include an image(i.e., the white portions at the top of the screen) of the targetingcannula as well as images (i.e., the white portion in the brain region)of the substance infused into the brain. The screen shot of FIG. 17A wascaptured at a first time in the procedure and the screen shot of FIG.17B was captured at a second subsequent time during the procedure. Thedistribution and dispersion pattern of the infused substance in thebrain, as well as the change in the distribution and dispersion patternof the infused substance in the brain, can be readily appreciated andtracked by reference to the screen shots of FIGS. 17A and 17B.

Other systems, methods, and/or computer program products according toembodiments of the invention will be or become apparent to one withskill in the art upon review of the following drawings and detaileddescription. It is intended that all such additional systems, methods,and/or computer program products be included within this description, bewithin the scope of the present invention, and be protected by theaccompanying claims.

In the drawings and specification, there have been disclosed embodimentsof the invention and, although specific terms are employed, they areused in a generic and descriptive sense only and not for purposes oflimitation, the scope of the invention being set forth in the followingclaims. Thus, the foregoing is illustrative of the present invention andis not to be construed as limiting thereof. More particularly, theworkflow steps may be carried out in a different manner, in a differentorder and/or with other workflow steps or may omit some or replace someworkflow steps with other steps. Although a few exemplary embodiments ofthis invention have been described, those skilled in the art willreadily appreciate that many modifications are possible in the exemplaryembodiments without materially departing from the novel teachings andadvantages of this invention. Accordingly, all such modifications areintended to be included within the scope of this invention as defined inthe claims. In the claims, means-plus-function clauses, where used, areintended to cover the structures described herein as performing therecited function and not only structural equivalents but also equivalentstructures. Therefore, it is to be understood that the foregoing isillustrative of the present invention and is not to be construed aslimited to the specific embodiments disclosed, and that modifications tothe disclosed embodiments, as well as other embodiments, are intended tobe included within the scope of the appended claims. The invention isdefined by the following claims, with equivalents of the claims to beincluded therein.

That which is claimed is:
 1. A cannula for transferring a substance toand/or from a patient, the cannula comprising: a rigid tubular supportsleeve defining a lumen extending from an inlet opening at a proximalend of the tubular support sleeve to an exit opening at a distal end ofthe tubular support sleeve; a transfer tube positioned in the lumen andextending fully through the inlet opening, the lumen and the exitopening, the transfer tube including a proximal extension sectionextending beyond the proximal end of the tubular support sleeve and adistal extension section extending beyond the distal end of the tubularsupport sleeve; and an inner sleeve disposed in the tubular supportsleeve and extending beyond the distal end of the tubular supportsleeve, wherein the transfer tube has a length that is greater than thatof the tubular support sleeve, the transfer tube extends fully throughthe inner sleeve, the proximal extension section extends beyond aproximal end of the inner sleeve, and the distal extension sectionextends beyond a distal end of the inner sleeve; wherein the tubularsupport sleeve comprises a rigid, MRI-compatible material; wherein thetransfer tube is adhered with adhesive to an inner surface of the innersleeve; and wherein: the transfer tube has an exit opening at a distalend of the distal extension section of the transfer tube and from whichthe substance is dispensed in use; an exterior surface of the cannulahas at least first, second and third co-axially disposed segments, anouter diameter of the second segment being greater than an outerdiameter of the first segment and an outer diameter of the third segmentbeing greater than the outer diameter of the second segment; the firstsegment extends from the distal end of the distal extension section ofthe transfer tube; the second segment extends between and adjoins eachof the first and third segments; the second segment includes a first endface defining a first step between the first segment and the secondsegment, the first end face projecting radially outwardly beyond theouter diameter of the first segment; the third segment includes a secondend face defining a second step between the second segment and the thirdsegment, the second end face projecting radially outwardly beyond theouter diameter of the second segment; and the third segment is longerthan each of the first and second segments.
 2. The cannula of claim 1wherein the tubular support sleeve comprises a ceramic material.
 3. Thecannula of claim 2 including a conformal polymeric sleeve surroundingthe tubular support sleeve.
 4. The cannula of claim 3 wherein theconformal polymeric sleeve is an elastomeric shrink tubing.
 5. Thecannula of claim 1 including a conformal polymeric sleeve surroundingthe tubular support sleeve.
 6. The cannula of claim 5 wherein theconformal polymeric sleeve is an elastomeric shrink tubing.
 7. Thecannula of claim 5 wherein the conformal polymeric sleeve extendssubstantially coextensive with the tubular support sleeve from theproximal end of the tubular support sleeve to the distal end of thetubular support sleeve.
 8. The cannula of claim 1 wherein the exteriorsurface includes a tapered transition between the third and secondsegments.
 9. The cannula of claim 1 wherein the transfer tube is formedof fused silica.
 10. The cannula of claim 1 wherein the tubular supportsleeve has a length of at least 10 inches.
 11. The cannula of claim 1wherein an outer surface of the tubular support sleeve has a size andgeometry adapted for use with a stereotactic frame.
 12. The cannula ofclaim 1 including a silicone or polyvinyl chloride (PVC) protectivetubing extending from the proximal end of the tubular support sleeve,wherein the proximal extension section of the transfer tube extendsthrough the protective tubing.
 13. The cannula of claim 12 wherein theprotective tubing is bonded to the proximal end of the tubular supportsleeve.
 14. The cannula of claim 1 wherein the transfer tube is acontinuous unitary tube formed of fused silica.
 15. The cannula of claim1 wherein: the first end face is the distal end of the inner sleeve; thesecond end face is the distal end of the tubular support sleeve; thefirst segment extends from the distal end of the distal extensionsection of the transfer tube to the distal end of the inner sleeve; thesecond segment extends from the distal end of the inner sleeve to thedistal end of the tubular support sleeve; and the tubular support sleeveincludes a tapered transition from the distal end of the tubular supportsleeve to an outer diameter of the tubular support sleeve.
 16. Thecannula of claim 1 wherein the inner sleeve is formed of a substantiallyrigid material.
 17. The cannula of claim 16 wherein the inner sleeve isadhered with adhesive to an inner surface of the tubular support sleeve.18. The cannula of claim 17 wherein: the cannula includes a conformalpolymeric sleeve surrounding the tubular support sleeve; the conformalpolymeric sleeve extends substantially coextensive with the tubularsupport sleeve from the proximal end of the tubular support sleeve tothe distal end of the tubular support sleeve; and the tubular supportsleeve comprises a ceramic material.
 19. The cannula of claim 1 whereinthe inner sleeve is adhered with adhesive to an inner surface of thetubular support sleeve to thereby increase a stiffness of the cannula.